Tetrahydrofuran → Methyl 2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxylate

HRID 2068266Notes

Reaction equation

HRID 2068266 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][CH:11]([C:15]([O:17][CH3:18])=[O:16])[CH2:10]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:29]1[CH2:33]OC[CH2:30]1>>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[CH2:10][C:11]2([C:15]([O:17][CH3:18])=[O:16])[CH2:30][CH2:29][CH2:33][CH:12]2[C:13]1=[O:14]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2733832Lithium Hexamethyldisilazide2×HCID 58218773Methyl 1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylate

Product 1

HCID 58218817Methyl 2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxylateYield 32%

Conditions

Temperature
-40 °C

Procedure

To methyl 1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylate (1.5 g, 6.1 mmol) dissolved in 5 mL anhydrous THF and cooled to −40° C., lithium bis(trimethylsily)amide (1.0 M in THF, 6.1 mL, 6.1 mmol) was added with a syringe. After stirring for 10 min, the bath was replaced with a 0° C. bath and stirring continued for another 10 min. The reaction mixture was then cooled to −40° C. and another 6.1 mL of lithium bis(trimethylsily)amide solution (6.1 mmol) was added. After stirring for 10 min at −40° C., the reaction mixture was allowed to gradually warm to room temperature, quenched with saturated ammonium chloride solution (15 ml) and the crude product was extracted with ether. The combined organic layer was dried over anhydrous Na2SO4, the solvent was evaporated and the residue purified by flash chromatography (SiO2, 10-100% EtOAc/hexanes) to yield 920 mg of methyl 2-(2,6-dimethylphenyl)-1-oxooctahydrocyclopenta[c]pyrrole-3a-carboxylate (32% yield). LC-MS Rt (retention time): 2.12 min, MS: (ES) m/z 288 (M+H+).

Workup

  1. customwas replaced with a 0° C.
  2. stirringstirring
  3. waitcontinued for another 10 min
  4. temperatureThe reaction mixture was then cooled to −40° C.
  5. stirringAfter stirring for 10 min at −40° C.
  6. temperatureto gradually warm to room temperature
  7. customquenched with saturated ammonium chloride solution (15 ml)
  8. extractionthe crude product was extracted with ether
  9. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  10. customthe solvent was evaporated
  11. customthe residue purified by flash chromatography (SiO2, 10-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f07c778d41bb4be7aac2e1c5bd986fdf
Source dataset
uspto-grants-2012_10
Patent number
US08293925B2

Reaction notes

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